<p>The chronic lymphocytic leukemia (CLL) treatment landscape has evolved substantially with the development of oral small-molecule agents. While these drugs have shown excellent clinical efficacy, concerns remain regarding treatment adherence in patients treated outside of clinical trials.</p>

Every time we introduce a new treatment, it brings new challenges. With oral therapy for CLL, there are several aspects to tackle. The first is education. At The University of Texas MD Anderson Cancer Center, we have a virtual clinic that offers counseling for patients on oral medication and is managed by our clinical pharmacist. They call patients when they start treatment and stay in touch to follow their adherence and to discuss any side effects. When we initiate treatment, we stress to patients the importance of adhering to the prescribed dose and taking the medication around the same time every day. We also have an in-depth education session about the most common side effects so that patients know what to expect in terms of potential toxicities. In addition, we remind patients to inform us if there are changes in other medications they are taking so that drug-drug interactions can be reviewed and doses can be adjusted as needed.

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We also add a component of individualization by trying to match patients with CLL with the best treatment schedule for them. Some of the oral agents can be given once or twice per day. For a younger patient, I will opt for a once-daily agent if I have that option. On the other hand, older patients are often accustomed to taking more than 1 medication multiple times per day, and, therefore, twice-a-day dosing is well accepted. We know that many patients with CLL have chronic comorbidities for which they are already taking medications. A 2024 study found that when an oral agent for CLL was administered to patients who were already receiving other medications for other chronic medical conditions, patients maintained good adherence to the medications for their chronic medical conditions. However, we know that no one has perfect medication adherence, even if a patient self-reports excellent adherence. An informative study on this issue was conducted in patients with chronic myeloid leukemia. In this study, which was published in 2010, Marin et al used a microelectronic monitoring system in pill bottle caps to track adherence in patients taking imatinib over 3 months. The researchers found that 26.4% of patients had an adherence of less than or equal to 90% of the intended dose, which negatively correlated to the 6-year probability of a major molecular response and a complete molecular response.

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The importance of the dose intensity of ibrutinib was studied in the RESONATE trial and was shown to affect progression-free survival, further supporting the importance of optimizing adherence. I think that our next step to improve adherence is to use technology. I often ask my patients to set up a simple cell phone alert to remind them to take their medication, but there are more sophisticated options on the market, such as automatic pill dispensers that send an alert to the patient and their caregiver and have systems built in to require the patient to confirm that they have taken their medication. These more sophisticated systems have really been key to improve adherence in some patients who have mild cognitive difficulties.